A mammalian-specific Alex3/Gαq protein complex regulates mitochondrial trafficking, dendritic complexity, and neuronal survival.
Sci Signal
; 17(822): eabq1007, 2024 02 06.
Article
em En
| MEDLINE
| ID: mdl-38320000
ABSTRACT
Mitochondrial dynamics and trafficking are essential to provide the energy required for neurotransmission and neural activity. We investigated how G protein-coupled receptors (GPCRs) and G proteins control mitochondrial dynamics and trafficking. The activation of Gαq inhibited mitochondrial trafficking in neurons through a mechanism that was independent of the canonical downstream PLCß pathway. Mitoproteome analysis revealed that Gαq interacted with the Eutherian-specific mitochondrial protein armadillo repeat-containing X-linked protein 3 (Alex3) and the Miro1/Trak2 complex, which acts as an adaptor for motor proteins involved in mitochondrial trafficking along dendrites and axons. By generating a CNS-specific Alex3 knockout mouse line, we demonstrated that Alex3 was required for the effects of Gαq on mitochondrial trafficking and dendritic growth in neurons. Alex3-deficient mice had altered amounts of ER stress response proteins, increased neuronal death, motor neuron loss, and severe motor deficits. These data revealed a mammalian-specific Alex3/Gαq mitochondrial complex, which enables control of mitochondrial trafficking and neuronal death by GPCRs.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Axônios
/
Neurônios
Limite:
Animals
Idioma:
En
Revista:
Sci Signal
/
Sci. signal
/
Science signaling
Assunto da revista:
CIENCIA
/
FISIOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Espanha